Humans are facing various problems not seen before due to the advent of an aging society caused by a prolonged average life span. In socio-economic aspects, the elderly sustenance allowance per head is expected to increase due to the increase in the elderly population and the reduction in the productive age population, and the interest in the improvement of the quality of life of the elderly is also a growing trend. As the social demands for the healthy and happy life of the elderly increase as described above, studies on the change in aging-related disease aspect and prevention of aging-related diseases are under active progress.
The aging process causes a wide variety of changes. Various changes appear, including reduced functions of respective main tissues, food intake and digestive disorders, reduced brain functions including defective memory, and reduced cardiovascular functions, as well as various appearance changes, such as skin wrinkles, hair decoloration, spine curving, and the change in motion. Moreover, these changes induce the reduction of functions and diseases of the respective tissues, and therefore, it is very important to understand causes of the reduction of external and internal functions due to aging and develop techniques of regulating the functions.
Besides, one of the large changes in functions due to aging is the reduction in immune function. This is called immunosenescence. When pathogens invade a host, the host defection action is made by two immune systems, an innate immune system and an adaptive immune system. Of these, the innate immune system is activated immediately after infection, to promptly regulate infecting pathogens, and takes charge of the initial infection until the adaptive immune system is activated. In this innate immune system, a receptor recognizing “pathogen associated molecular patterns (PAMPs) existing in the pathogens is called “pattern recognition receptors (PRRs), and these receptors are called toll-like receptors in a mammal. So far, 13 kinds of TLRs have been found, and studies on agonists of the respective TLRs have been actively conducted (Shizuo Akira et al, Cell, Pathogen Recognition and Innate Immunity, 124(4):783-801, 2006). PRRs like TLRs exist on the cell surface or in the protoplasm, and have been known to regulate the innate immune response by various stimuli of PAMPs, and further regulate the adaptive immune response. Therefore, the agonists of TLRs may be target materials suitable for the development of various immunomodulators and vaccine adjuvants.
Of studies on aging, the fields that have received the most attention so far are the life span adjustment of aging or functional recovery of aging. Recently, studies on the extension of life span are rapidly increasing through various methods, such as by inhibiting the expression of a particular gene or overexpressing the particular gene in studies using drosophila models or nematodes, restricting diet, or treating with rapamycin. In addition, the interest in the maintenance of functions or recovery of functions, instead of the simple extension of life span, is also a growing trend. However, the regulation of a particular gene referring to the results shown in lower animal models may cause other functional side effects, and thus has a limitation in the application to humans. Moreover, the treatment with a drug, such as rapamycin, may greatly influence the immune function.
Throughout this application, various patents and publications are referenced, and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.